study to assess the safety, tolerability, and pharmacodynamics of rta 402 in patients with hepatic dysfunction

Conditions: Liver Disease

Summary: this study assesses the safety and tolerability of rta 402 in patients with liver disease.

rta 402 is a synthetic triterpenoid that is designed to suppress oxidative stress and inflammatory processes that play a significant role in a wide variety of diseases. it is a potent suppressor of inflammation and oxidative stress. oxidative stress plays a role in the pathogenesis of hepatitis, and rta 402 has demonstrated activity in a preclinical model of hepatitis, in addition to other models of inflammation. this is a 28-day, multiple-dose, dose-escalation study. it is anticipated that a total of 3 groups of 8 patients each will be enrolled, in which 6 patients in each group will be randomized to receive rta 402, and 2 patients per group will be randomized to placebo (3:1). patients will receive treatment daily for 14 days with a starting dose of 5mg, 25mg, or 50mg. patients will return for follow up visits on days 16 and 21, and complete end of study procedures on day 28.

Eligibility criteria:
inclusion criteria: * chronic liver disease. * an estimated creatinine clearance of ≥ 60 ml/min. * serum alanine transaminase (alt) or aspartate transaminase (ast) elevation must be above the upper limit of normal and below 5 times the upper limit of normal for patients with underlying liver disease; child-pugh score 5 to 9 (mild to moderate impairment). * patient must agree to practice effective contraception during the entire study period. * patient is willing to avoid strenuous physical activity from 24 hours prior to the study start, throughout the study, and for 2 weeks after the administration of the dose of study drug * patient is willing to avoid any alcohol consumption for the 24 hours prior to, and the 48 hours after administration of study drug; and avoid excessive alcohol consumption for the duration of the follow-up period. * patient must be able and willing to sign informed consent form. exclusion criteria: * patient with clinically significant illnesses or recent hospitalization (within 60 days) which could compromise participation in the study in the judgment of the investigator, including: uncontrolled diabetes; active or uncontrolled infection; confirmed diagnosis of hiv infection; uncontrolled hypertension, symptomatic congestive heart failure, unstable angina pectoris, myocardial infarction within the past 6 months, or uncontrolled cardiac arrhythmia. * patient with any other auto immune disease, major chronic inflammatory disease or syndrome requiring significant treatment within the past year. * patients who are pregnant or breast feeding * patient receiving or has received any investigational drug within 30 days prior (or is currently using an investigational device) * patients with prior (within 4 weeks) or concurrent treatment with oral steroids, or protein-based therapy (i.e. tnfa) * patients with positive urine screen for drugs of abuse except when receiving a prescribed medication for a known indication * patients with grade 2 or above hepatic encephalopathy. * patients who donated blood or experienced a significant blood loss (\>450 ml) within 8 weeks of screening * patients with a history of bleeding varices within 12 weeks of screening. * patients with psychiatric illness or other condition that would limit compliance with study requirements.